The prevention and treatment of cardiac arrhythmias in pediatric patients is of increasing concern as more children with cardiac disease are diagnosed and undergo medical and surgical treatment. The purpose of the proposed studies is to determine the mechanisms responsible for cardiac arrhythmias in children and the means for their prevention and treatment. The mission is divided into a series of interrelated projects and will utilize the skills of investigators in cardiac electrophysiology and pharmacology, pediatric clinical pharmacology, pediatric cardiology, pathology and biochemistry. In one project we will determine the relationship of P wave abnormalities and cardiac arrhythmias to the clinical source and clinical pathology of atrial disease in children. This information will be correlated with the cellular electrophysiologic and and ultrastructural characteristics of atrial tissues and with drug response. To permit a completely systematic correlation of the relationship between atrial size and clinical pathology with cellular electrophysiologic and ultrastructural changes, we will also study atrial arrhythmias in a canine model. In other projects we will study the clinical pharmacology of the cardioactive drugs used to treat arrhymias in children, and use techniques for cellular electrophysiologic and in situ cardiac studies to investigate the rlationship between development (fetus through adult) and electrophysiologic characteristics, ultrastructures and pharmacologic responses. In another project we will use biochemical techniques to study the development characteristics of cardiac autonomic control mechanisms. Lastly a clinical pharmacology core laboratory is proposed, which will measure plasma and urine drug concentrations for this Mission and eventually for other Missions in the Program. These studies will provide a multidisciplinary approach to identification of the mechanisms responsible for arrhythmias in children as well as means for their prevention and treatment.